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    DRUG:

    AZD9574

    i
    Other names: AZD9574, AZD 9574, AZD-9574
    Company:
    AstraZeneca
    Drug class:
    PARP1 inhibitor
    Related drugs:
    10d
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=695, Recruiting, AstraZeneca | Trial completion date: Apr 2027 --> Aug 2027 | Trial primary completion date: Apr 2027 --> Aug 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574
    11d
    A novel 18 F-labeled brain penetrant PET ligand for imaging poly(ADP-ribose) polymerase-1. (PubMed, bioRxiv)
    In 22Rv1 xenograft mouse models, the tracer demonstrated significant tumor accumulation that was specific to PARP-1, and ex vivo biodistribution confirmed organ uptake consistent with specific tumor binding and PARP-1 expression. Together, these findings establish [ 18 F]AZD9574 as a promising PARP-1-targeted imaging agent with strong potential for advancing cancer research and therapeutic monitoring.
    Journal • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    AZD9574
    2ms
    SEACLIFF: Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1/2, N=177, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open
    |
    STEAP1 (STEAP Family Member 1)
    |
    AZD9574
    2ms
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=695, Recruiting, AstraZeneca | Trial completion date: Feb 2027 --> Jun 2027 | Trial primary completion date: Feb 2027 --> Jun 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574
    3ms
    SEACLIFF: Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer (clinicaltrials.gov)
    P1/2, N=177, Not yet recruiting, AstraZeneca
    New P1/2 trial
    |
    STEAP1 (STEAP Family Member 1)
    |
    AZD9574
    8ms
    H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition. (PubMed, Neuro Oncol)
    The HRR deficiency in H3K27M DMG can be therapeutically leveraged with PARP inhibitors to radiosensitize and induce an NK cell-mediated antitumor immune response selectively in H3K27M DMG, supporting the clinical investigation of PARP1 inhibitors with RT in DMG patients.
    Journal • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • NKG2D (killer cell lectin like receptor K1)
    |
    Lynparza (olaparib) • AZD9574
    8ms
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial completion date: Aug 2026 --> Feb 2027 | Trial primary completion date: Aug 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574
    11ms
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Jan 2026 --> Aug 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574
    1year
    Discovery of Pyrazolo[1,5,4-de]quinoxalin-2(3H)-one Derivatives as Highly Potent and Selective PARP1 Inhibitors. (PubMed, J Med Chem)
    30 achieved tumor regression in the BRCA1-mutated MDA-MB-436 xenograft model and showed synergistic efficacy in combination with carboplatin in the SUM149PT xenograft model. In the rat hematological toxicity study, 30 exhibited minimal impact on hematological parameters at 25 mg/kg, while AZD5305 at 1 mg/kg caused 56.5% reduction of reticulocyte. Taken together, we discovered compound 30 with a therapeutic index superior to that of PARP1 inhibitors AZD5305 and AZD9574 in the preclinical setting.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    BRCA1 mutation • HRD • HRD + BRCA1 mutation
    |
    carboplatin • saruparib (AZD5305) • AZD9574
    1year
    H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition. (PubMed, bioRxiv)
    We also show that the novel brain penetrant, PARP1-selective inhibitor AZD9574 compares favorably to olaparib when combined with RT, prolonging survival in a syngeneic orthotopic model of H3K27M DMG. This study highlights the ability of PARP1 inhibition to radiosensitize and induce an NK cell-mediated antitumor immunity in H3K27M DMG and supports future clinical investigation.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • NKG2D (killer cell lectin like receptor K1) • RNF168 (Ring Finger Protein 168)
    |
    Lynparza (olaparib) • AZD9574
    over1year
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial primary completion date: Apr 2025 --> Jan 2026
    Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574